Identification of dihydropteridine reductase in human platelets

Normal human platelets were shown to contain the enzyme dihydropteridine reductase. The enzyme was not found in a variety of other cells of hematogenous origin. Partial purification and kinetic and physical data indicated that the platelet enzyme is similar to that previously characterized from liver. Dihydropteridine reductase is important for the regeneration of tetrahydrobiopterin, a required cofactor in hydroxylation reactions involved in biogenic amine formation. The presence of the enzyme may indicate that some synthesis de novo of serotonin and/or catecholamines occurs in platelets, as opposed to a purely storage and transport function. In addition, screening for hyperphenylalaninemia due to dihydropteridine reductase deficiency may become feasible by assaying platelets for enzyme activity.     

Dynamics of Ventricular Repolarization in Patients with Dilated Cardiomyopathy Versus Healthy Subjects

Background: Patients with impaired left ventricular function have a high risk of developing ventricular arrhythmias and sudden death. Among different markers of risk, the prolongation and regional heterogeneity of repolarization are of increasing interest. However, there are limited data regarding feasibility of analyzing repolarization parameters and their dynamics in 24‐hour Holter ECG recordings. Methods: Dynamic behavior of repolarization parameters was studied with a new automatic algorithm in digital 24‐hour Holter recordings of 60 healthy subjects and 55 patients with idiopathic dilated cardiomyopathy (IDC). Repolarization parameters included the mean value of QT and QTc durations, QT dispersion, and peaks of QT duration and QT dispersion above prespecified thresholds. Results: In comparison to healthy subjects, patients with IDC had lower heart rate variability, longer mean QT and QTc durations, higher content of QTc peaks >500 ms, longer QT dispersion and its standard deviation, and a higher content of peaks >100 ms of QT dispersion (P < 0.01 for all comparisons). These repolarization parameters were significantly higher in IDC patients after adjustment for age, sex, and heart rate variability. The parameters of repolarization dynamics correlated with SDNN in healthy subjects but not in dilated cardiomyopathy patients. Conclusions: The automatic assessment of repolarization parameters in 24‐hour digital ECG recordings is feasible and differentiates dilated cardiomyopathy patients from healthy subjects. Patients with dilated cardiomyopathy have increased QT duration, QT dispersion, and increased variability of QT dispersion reflecting variations in T‐wave morphology, the factors which might predispose them to the development of arrhythmic events.     

Near-infrared spectroscopic imaging of the whole hand: A new tool to assess tissue perfusion and peripheral microcirculation in scleroderma

Objectives

Systemic sclerosis (SSc) causes functional and structural microcirculatory dysfunction, affecting also distal extremities. Optical Near-InfraRed Spectroscopy (NIRS) of blood HbO₂ saturation (stO₂) is able to evaluate O₂ delivery/consumption balance in the explored tissue. The NIRS-sensitive camera non-invasively detects stO₂ values in superficial tissues, automatically generating 2D-imaging maps in real time. We aimed at testing whether NIRS hand imaging may evaluate peripheral microcirculatory dysfunction and its spatial heterogeneity in SSc patients compared to controls.

Coronary endarterectomy and bypass grafting without cardiopulmonary bypass

We prospectively analyzed patients who underwent simultaneous off-pump coronary artery bypass grafting and endarterectomy between March 1, 1997 and February 28, 2002. The incidence of perioperative myocardial infarction, need for inotropic support, morbidity, long-time functional class, and mortality were evaluated.Nine endarterectomies were performed in eight patients, more frequently in the right coronary artery. Dopamine was used in four patients. One perioperative myocardial infarction (12.5%) occurred. No deaths occurred and all patients are now functional class I. Tests for ischemia have been negative in all patients.Coronary endarterectomy is an alternative procedure that has little morbidity and enables complete myocardial revascularization without cardiopulmonary bypass.     

Impact of Race and Socioeconomic Status on Outcomes in Patients Hospitalized with COVID-19

BackgroundThe impact of race and socioeconomic status on clinical outcomes has not been quantified in patients hospitalized with coronavirus disease 2019 (COVID-19).ObjectiveTo evaluate the association between patient sociodemographics and neighborhood disadvantage with frequencies of death, invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission in patients hospitalized with COVID-19.DesignRetrospective cohort study.SettingFour hospitals in an integrated health system serving southeast Michigan.ParticipantsAdult patients admitted to the hospital with a COVID-19 diagnosis confirmed by polymerase chain reaction.Main MeasuresPatient sociodemographics, comorbidities, and clinical outcomes were collected. Neighborhood socioeconomic variables were obtained at the census tract level from the 2018 American Community Survey. Relationships between neighborhood median income and clinical outcomes were evaluated using multivariate logistic regression models, controlling for patient age, sex, race, Charlson Comorbidity Index, obesity, smoking status, and living environment.Key ResultsBlack patients lived in significantly poorer neighborhoods than White patients (median income: $34,758 (24,531–56,095) vs. $63,317 (49,850–85,776), p < 0.001) and were more likely to have Medicaid insurance (19.4% vs. 11.2%, p < 0.001). Patients from neighborhoods with lower median income were significantly more likely to require IMV (lowest quartile: 25.4%, highest quartile: 16.0%, p < 0.001) and ICU admission (35.2%, 19.9%, p < 0.001). After adjusting for age, sex, race, and comorbidities, higher neighborhood income ($10,000 increase) remained a significant negative predictor for IMV (OR: 0.95 (95% CI 0.91, 0.99), p = 0.02) and ICU admission (OR: 0.92 (95% CI 0.89, 0.96), p < 0.001).ConclusionsNeighborhood disadvantage, which is closely associated with race, is a predictor of poor clinical outcomes in COVID-19. Measures of neighborhood disadvantage should be used to inform policies that aim to reduce COVID-19 disparities in the Black community.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06527-1.KEY WORDS: COVID-19, disparities, disadvantage, socioeconomic status, race     

Neuroendocrine regulation of adrenal 5'-monodeiodination during acute cold exposure in the rat. I. Effects of hypophysectomy

Circulating levels of T4, T3, corticosterone, noradrenaline, and adrenaline, as well as 5'-monodeiodinase activity (5'-MA) were measured in control and hypophysectomized rats acutely exposed to cold environment (15-120 min, 4 C). In addition to the well known activation of the sympathoadrenomedullary system and the hypothalamic-pituitary-adrenal and-thyroid axes, cold exposure was followed by a rapid and sustained increase of 5'-MA in the hypothalamus, and a byphasic course of activation in the adrenal gland in control rats. The adrenal rapid activation (30 min) corresponded to the medulla and the slower activation (120 min) to the cortex. Both, the basal adrenal 5'-MA and the response to cold in adrenal and hypothalamus were 2-fold higher in hypophysectomized rats compared to control. The time course of enzyme activation in these structures suggests that: 1) organ-specific increases in 5'-MA may be associated to a simultaneous rise in their metabolic and/or functional activity, 2) the triggering mechanisms involves an immediate sympathetic signal activating the hypothalamic-adrenal medulla response and a pituitary signal eliciting a slower adrenocortical response, and 3) the compensatory sympathetic hyperactivity after panhypopituitarism contribute to enhance both the adrenal enzyme basal activity and the hypothalamic and adrenal hyperresponse to cold stress.     

Physiologically stable F127-GO supramolecular hydrogel with sustained drug release characteristic for chemotherapy and photothermal therapy

A synthetic method for preparing a Pluronic F127 (F127)-stabilized graphene (GO) supramolecular hydrogel as a safe nanovehicle for combination treatment has been studied. Doxorubicin (DOX) as a model drug is non-covalently bound on the great surface area of GO due to strong π–π interaction, hydrophobic interaction, and the strongest hydrogen bonding. In vitro drug release experiments revealed that this F127-stabilized GO supramolecular hydrogel has a sustained drug release characteristic. Furthermore, the supramolecular hydrogel showed better in vitro antitumor ability under NIR (near infrared) laser irradiation because of the excellent photothermal effect of GO. Moreover, we evaluated its antitumor ability in vivo and the results show that the hydrogel system can also markedly inhibit the growth of a tumor when administered individually, especially under laser irradiation. All these findings make the supramolecular hydrogel system promising for combination therapy with good bioavailability and minimal side effects.

The F127-GO-DOX supramolecular hydrogel system with sustained drug release characteristic for chemotherapy and photothermal therapy.     

Survival and mortality among users and non-users of hydroxyurea with sickle cell disease

OBJECTIVE:

to estimate survival, mortality and cause of death among users or not of hydroxyurea with sickle cell disease.

METHOD:

cohort study with retrospective data collection, from 1980 to 2010 of patients receiving inpatient treatment in two Brazilian public hospitals. The survival probability was determined using the Kaplan-Meier estimator, survival calculations (SPSS version 10.0), comparison between survival curves, using the log rank method. The level of significance was p=0.05.

RESULTS:

of 63 patients, 87% had sickle cell anemia, with 39 using hydroxyurea, with a mean time of use of the drug of 20.0±10.0 years and a mean dose of 17.37±5.4 to 20.94±7.2 mg/kg/day, raising the fetal hemoglobin. In the comparison between those using hydroxyurea and those not, the survival curve was greater among the users (p=0.014). A total of 10 deaths occurred, with a mean age of 28.1 years old, and with Acute Respiratory Failure as the main cause.

CONCLUSION:

the survival curve is greater among the users of hydroxyurea. The results indicate the importance of the nurse incorporating therapeutic advances of hydroxyurea in her care actions.